Tag Archives: Dm2

Most of the emphasis on myotonic dystrophy has been on DM1 or Myotonic Dystrophy Type 1 Now a new generous gift will push the reseach front on DM2! A great day!

Gift Will Advance Research on Myotonic Dystrophy Type 2

September 09, 2014

Generous Donors!

Albert (Alfy) and Lilyan (Lil) Nathan

A $1.25 million gift from Lilyan (Lil) and Albert (Alfy) Nathan of Florida and Michael and Sherry Goldberg of Chicago will create a new center dedicated to research on myotonic dystrophy type 2 (DM2) at the University of Rochester School of Medicine and Dentistry. The gift will be used to support a new research program that will be led by UR Medicine neurologist Chad Heatwole, M.D.

Scientists have revealed an atomic-level view of a genetic defect that causes a form of muscular dystrophy, myotonic dystrophy type 2, and have used this information to design drug candidates with potential to counter those defects—and reverse the disease.

Scientists from The Scripps Research Institute have revealed an atomic-level view of a genetic defect that causes a form of muscular dystrophy, myotonic dystrophy type 2, and have used this information to design drug candidates with potential to counter those defects — and reverse the disease.

“This the first time the structure of the RNA defect that causes this disease has been determined,” said TSRI Associate Professor Matthew Disney, who led the study. “Based on these results, we designed compounds that, even in small amounts, significantly improve disease-associated defects in treated cells.”

Myotonic dystrophy type 2 is a relatively rare form of muscular dystrophy that is somewhat milder than myotonic dystrophy type 1, the most common adult-onset form of the disease.

Both types of myotonic dystrophy are inherited disorders that involve progressive muscle wasting and weakness, and both are caused by a type of genetic defect known as a “RNA repeat expansion,” a series of nucleotides repeated more times than normal in an individual’s genetic code. The repeat binds to the protein MBNL1, rendering it inactive and resulting in RNA splicing abnormalities — which lead to the disease.

Many other researchers had tried to find the atomic-level structure of the myotonic dystrophy 2 repeat, but had run into technical difficulties. In a technique called X-ray crystallography, which is used to find detailed structural information, scientists manipulate a molecule so that a crystal forms. This crystal is then placed in a beam of X-rays, which diffract when they strike the atoms in the crystal. Based on the pattern of diffraction, scientists can then reconstruct the shape of the original molecule.

Prior to the new research, which was published in an advance, online issue of the journal ACS Chemical Biology, scientists had not been able to crystallize the problematic RNA. The Scripps Florida team spent several years on the problem and succeeded in engineering the RNA to have crystal contacts in different positions. This allowed the RNA to be crystallized — and its structure to be revealed.

Using information about the RNA’s structure and movement, the scientists were able to design molecules to improve RNA function.

The new findings were confirmed using sophisticated computational models that show precisely how the small molecules interact with and alter the RNA structure over time. Those predictive models matched what the scientists found in the study — that these new compounds bind to the repeat structure in a predictable and easily reproducible way, attacking the cause of the disease.

“We used a bottom-up approach, by first understanding how the small components of the RNA structure interact with small molecules,” said Jessica Childs-Disney of TSRI, who was first author of the paper with Ilyas Yildirim of Northwestern University. “The fact that our compounds improve the defects shows that our unconventional approach works.”

So whats it like living with Myotonic Dystrophy? It’s a highly variable and complex disease so each person’s journey is different. There are some commonalities. A study was done a ways back to see how couples coped with the disease. This study can be helpful for families with the disease, and extended families to help them see the disease and to provide more support. A common theme is that the couple seems to have to find their own way, that there is not one entity that can point them in the right direction. Even family and friends need help and direction in understanding the disease. This article is easier to read than most medical articles.

The Muscular Dystrophy Association of the USA (MDA) announced its winter research grants. 13.6 million was awarded including two grants for Myotonic Dystrophy research. One grant to doctor Disney will explore the possible therapeutic effects of small molecule approach for DM2. This would be a strong complement to the DM1 research that is ongoing in his lab.

The other grant to Dr. Mockton is to research the effect of Triplet expansion and stability on the likely course of the Myotonic Dystrophy Disease.

MDA is spending 4.6 of its research grant budget this winter on Myotonic Dystrophy Research.

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This is a diagram or the major effects of Myotonic Dystrophy on the Human. Click to enlarge

The Blog. You’ve reached this site as you may be the one of nearly one million people affected by Myotonic Dystrophy Worldwide. This site aggregates and publishes all information on Myotonic Dystrophy Myotonic Dystrophy is a disease that is genetically based and inherited from one generation to the next. One out of two children of a person with myotonic dystrophy will most likely have the disease. Unlike most diseases, the symptoms that a person with this disease varies from person to person. Some people are just mildly affected others are severely affected. This makes it hard to tell you exactly how the disease will affect a particular person.

Four treatments that have potential have now surfaced about Myotonic Dystrophy. These are three approved Drugs by FDA and “off label use” may assist some people with DM1. (As always check with your Doctor) . The other is a drug that is not FDA approved in the USA for human use. Three off label uses have showed promise in mice studies but as yet there is no human data… In January of 2017 Ionis Pharmaceuticals stopped the trials of its DMPK-2.5Rx drug as it failed to show promise in the human trials.

NOTE: These potential treatments are just that potential. NO studies in humans have been completed and reported. However, more and more information is available and hereat this si you will find all that is published. You and your doctor should discuss these if you feel it warranted.

Myotonic dystrophy is a rare disease with an incidence of about one in 8000 in European and North American Populations. The incidence in Japan is approximately 1 in 20,000. In Africa and China the incidence is much lower. The incidence of the congenital form of myotonic dystrophy is much lower with an incidence of 1/100,000. A more recent study by Campbell in Canada put the incidence of the congenital form at 1/47,000 That means that most doctors will not have a patient with the disease in their practice. Thus, many people are turning to organizations like the Myotonic Dystrophy Foundation for help and assistance.